Our recent finding that streptococcal M protein has a striking physicochemical and primary structure similarity to rabbit skeletal muscle tropomyosin has prompted an investigation as to the significance of this homology with relation to rheumatic fever, cross-reactive antibodies, and the antiphagocytic property of M protein. Tropomyosin from normal and rheumatic human hearts will be isolated and cleaved by chemical and enzymatic methods. Selected peptides will be isolated, sequenced and compared to the sequence of M protein and rabbit tropomyosin to determine if closer homologies exist. Peptides will be used in radiocompetitive inhibition and radioimmunoassays to determine if the structural resemblance of M protein to tropomyosin plays a role in the formation of cross-reactive antibodies to muscle tissue. Smooth muscle tropomyosin will be compared by peptide map with human striated muscle tropomyosin to determine if differences occur. Differing peptides will be analyzed by sequence analysis. M protein's resemblance to tropomyosin may play a role in the antiphagocytic effect of the M molecule by blocking the actin polymerization mechanisms required for phagocytic function. The abilty of M protein to bind to actin or inhibit ATPase activity will be tested. The studies outlined should enable us to determine if the significant structural and physicochemical resemblance of M protein to mammalian tropomyosin exerts an effect on the ability of the group A streptococcus to cause disease.